Living organisms produce chemicals called natural products for defense and communication. Oftentimes, these chemicals, or similar derivatives, can be used by humans as drugs, and nearly 50% of all the prescription drugs that are in use today were derived from naturally occurring chemicals. Some of the most interesting and promising natural products are extremely potent and thus are produced in very low amounts. In order to identify natural products, it is necessary to obtain enough material to analytically characterize them using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. MS is a very sensitive technique, but it often does not provide enough information to fully identify an unknown molecule. NMR provides atomic level information that can be used to determine unknown structures, but it is very insensitive and thus requires a large amount of sample. This proposal seeks to improve the sensitivity of NMR measurements in order to reduce the sample requirements for natural product identification. The most cost-effective and practical technical improvement is in the design of the NMR probe, which provides the direct interface between the sample and the spectrometer. The overall goal of this proposal is to design, build, test, and commission a new cryogenically cooled probe with high temperature superconducting (HTS) material. By improving the technical designs of the coils, this probe will be optimized for 13C detection but will retain exceptional performance for 1H detection as well. The result will be nearly a 10-fold improvement in 13C mass sensitivity over the best currently available probe. It will also have a 1H mass sensitivity that is equal to, or greater than, the best currently available probe. The team of investigators that are collaborating on this proposal have previously worked together to build a 1-mm HTS cryogenically cooled probe, which currently has the greatest 1H mass sensitivity in the world. The new 13C- optimized probe will provide a significant technological leap in HTS probes and will enable many new studies in natural product discovery through large decreases in sample requirements. PUBLIC HEALTH RELEVANCE Many of drugs that humans take to cure diseases, especially cancer and microbial infections, are derived from living organisms. It is critical to continue to search for naturally occurring chemicals to provide new cures to disease. This proposal supports the development of technology to improve the efficiency of discovery of these important chemicals from nature.